TOKYO and PRINCETON, N.J., February 29, 2008 /PRNewswire/ --
Otsuka Pharmaceutical Co., Ltd. and Bristol-Myers Squibb Company
announced today that the U.S. Food and Drug Administration (FDA)
approved the supplemental New Drug Application for Abilify
(aripiprazole) for the acute treatment of manic and mixed episodes
associated with Bipolar I Disorder, with or without psychotic
features in pediatric patients (10 to 17 years old). Abilify has
been approved for the acute and maintenance treatment of manic and
mixed episodes associated with Bipolar I Disorder with or without
psychotic features in adults since September 2004 and March 2005,
respectively.

"Pediatric bipolar illness is a serious condition," said
Christoph Correll, M.D., Medical Director, Recognition and
Prevention Program, The Zucker Hillside Hospital and Assistant
Professor of Psychiatry and Behavioral Sciences, Albert Einstein
College of Medicine, Glen Oaks, New York. "The availability of an
additional treatment option that can help guide decisions in
managing Bipolar I Disorder in children and adolescents is welcome
news."

The approval is based on results from a four-week, multicenter,
randomized, double-blind, placebo-controlled study in pediatric
patients (10 to 17 years old) with Bipolar I Disorder that
demonstrated efficacy with Abilify compared to placebo on the
primary efficacy endpoint, mean change from baseline to Week 4 on
the Young-Mania Rating Scale (Y-MRS) Total Score.

"We are pleased that the FDA has approved Abilify to treat
pediatric patients aged 10 to 17 years suffering from Bipolar I
Disorder," said Taro Iwamoto, Ph.D., Chief Executive Officer,
President and Chief Operating Officer, Otsuka Pharmaceutical
Development and Commercialization, Inc. "The approval of this new
indication for Abilify provides clinicians with expanded treatment
options that can help address the therapeutic needs of this
population."

"We are committed to developing innovative new medicines to
their fullest potential," said Elliott Sigal, M.D., Ph.D.,
Executive Vice President, Chief Scientific Officer and President,
Research and Development, Bristol-Myers Squibb. "Expanding the
clinical use of an important therapy such as Abilify gives
pediatric patients with Bipolar I Disorder and their caregivers a
new treatment option in their fight against this serious
disease."

Clinical Trial Design and Findings

These findings are from a four-week, multicenter, randomized,
double-blind, placebo-controlled study, which evaluated the
efficacy and safety of Abilify in 296 pediatric patients (10 to 17
years old) with a DSM-IV diagnosis of Bipolar I Disorder, manic or
mixed episodes, with or without psychotic features. Diagnosis was
made by a trained child and adolescent psychiatrist and confirmed
by a separate diagnostic interview. This study was conducted on an
outpatient basis with the possibility of inpatient hospitalization,
as needed. This clinical trial was sponsored by Otsuka
Pharmaceutical Co., Ltd. and its U.S. subsidiary, Otsuka
Pharmaceutical Development & Commercialization, Inc.
(Princeton, NJ) with enrollment at 54 U.S. centers.

After a screening period of up to four weeks, pediatric patients
(10 to 17 years old) who scored greater than or equal to 20 on the
Y-MRS* were randomly assigned to receive one of two fixed doses of
Abilify [10 mg/day (n=98) or 30 mg/day (n=99)] or placebo (n=99).
Abilify was initiated at a starting dose of 2 mg/day and titrated
to the target dose of 10 mg/day or 30 mg/day.

The primary efficacy endpoint was the mean change in the Y-MRS
Total Score from baseline to Week 4. Safety evaluations included
incidence of adverse reactions, discontinuation due to adverse
reactions, laboratory measures and body weight.

For the primary endpoint, both doses of Abilify demonstrated
statistically significant improvement in symptoms when compared to
placebo (p-value less than 0.0001) as measured by the mean change
from baseline to endpoint (Week 4) on the Y-MRS Total Score. The
efficacy of Abilify for the maintenance treatment of Bipolar I
Disorder in the pediatric population has not been evaluated.

In the study, weight gain greater than or equal to 7% change
from baseline was seen in 3.2%, 9.4% and 3.3% for the Abilify 10
mg, Abilify 30 mg and placebo groups, respectively. The mean change
from baseline to Week 4 in body weight was 0.6 kilograms (kg) for
Abilify 10 mg, 0.9 kg for Abilify 30 mg and 0.5 kg for placebo.

In this study, Abilify demonstrated no clinically important
differences on prolactin and the following metabolic parameters:
triglyceride, HDL-C, LDL-C and total cholesterol. All treatment
groups showed a reduction in mean serum prolactin levels at last
visit relative to baseline.

About Abilify (aripiprazole)

The first and only available dopamine partial agonist, Abilify
is indicated for the treatment of acute manic or mixed episodes
associated with Bipolar I Disorder in adults and pediatric patients
(10 to 17 years old). Abilify (aripiprazole) Injection is
indicated for the treatment of adults with agitation associated
with Bipolar I Disorder, manic or mixed.

Initially approved in November 2002, over 14.9 million
prescriptions have been written for Abilify in the U.S.(2) through
December 2007.

Abilify is available by prescription only. Abilify Tablets
should be taken once daily with or without food and are available
in 2 mg, 5 mg, 10 mg, 15 mg, 20 mg and 30 mg strengths. Abilify
Discmelt (aripiprazole) Orally Disintegrating Tablets are
available in 10 mg and 15 mg strengths. In addition, Abilify is
available in a 1 mg/mL nonrefrigerated Oral Solution and as a
single-dose, ready-to-use solution for intramuscular injection 7.5
mg/mL. In adult patients, the recommended Abilify (aripiprazole)
Oral target dose is 15 mg/day to 30 mg/day in Bipolar I Disorder.
In pediatric patients (10 to 17 years old) with Bipolar I Disorder,
the recommended Abilify Oral target dose is 10 mg/day (with a
starting dose of 2 mg/day which was titrated to 5 mg/day after 2
days and to the target dose of 10 mg/day after 2 additional days).
In adult patients with agitation associated with bipolar mania, the
Abilify Injection initial dose is 9.75 mg/1.3 mL. If ongoing
Abilify therapy is clinically indicated, oral Abilify in a range of
10 mg/day to 30 mg/day should replace Abilify Injection as soon as
possible. The safety of doses of Abilify Oral or Abilify Injection
above 30 mg/day has not been evaluated in clinical trials.

Abilify Indications

Abilify is indicated for acute and maintenance treatment of adults with manic or mixed episodes associated with Bipolar I Disorder with or without psychotic features

Abilify is indicated for acute treatment of pediatric patients (10 to 17 years old) with manic or mixed episodes associated with Bipolar I Disorder with or without psychotic features

Abilify Injection is indicated for the treatment of adults with agitation associated with Bipolar I Disorder, manic or mixed.

Important Safety Information

Elderly patients with dementia-related psychosis treated with
atypical antipsychotic drugs are at an increased risk (1.6 to 1.7
times) of death compared to placebo (4.5% vs 2.6%, respectively).
Abilify is not approved for the treatment of patients with
dementia-related psychosis (see Boxed WARNING).

Antidepressants increased the risk compared to placebo of
suicidal thinking and behavior (suicidality) in children,
adolescents, and young adults in short-term studies of major
depressive disorder (MDD) and other psychiatric disorders. Anyone
considering the use of adjunctive Abilify or another antidepressant
in a child, adolescent, or young adult must balance this risk with
the clinical need. Short-term studies did not show an increased
risk of suicidality in adults beyond age 24. Depression and certain
other psychiatric disorders are themselves associated with
increases in the risk of suicide. Patients of all ages who are
started on antidepressant therapy should be monitored appropriately
and observed closely for clinical worsening, suicidality, or
unusual changes in behavior. Families and caregivers should be
advised for the need for close observation and communication with
the prescriber. Abilify is not approved for use in pediatric
patients with depression (See Boxed WARNING).

Contraindications: Known hypersensitivity reaction to Abilify.
Reactions have ranged from pruritus/urticaria to anaphylaxis.

As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with Abilify. NMS can cause hyperpyrexia, muscle rigidity, diaphoresis, tachycardia, irregular pulse or blood pressure, cardiac dysrhythmia, and altered mental status. If signs and symptoms appear, immediate discontinuation is recommended

Tardive dyskinesia (TD) -- The risk of developing TD and the potential for it to become irreversible may increase as the duration of treatment and the total cumulative dose increase. Prescribing should be consistent with the need to minimize TD. If signs and symptoms appear, discontinuation should be considered since TD may remit, partially or completely

Hyperglycemia and diabetes mellitus -- Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including Abilify. Patients with diabetes should be monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. There have been few reports of hyperglycemia with Abilify

Abilify may be associated with orthostatic hypotension and
should be used with caution in patients with known cardiovascular
disease, cerebrovascular disease, or conditions which would
predispose them to hypotension.

As with other antipsychotic drugs, Abilify should be used with
caution in patients with a history of seizures or with conditions
that lower the seizure threshold.

Like other antipsychotics, Abilify may have the potential to
impair judgment, thinking, or motor skills. Patients should not
drive or operate hazardous machinery until they are certain Abilify
does not affect them adversely.

Disruption of the body's ability to reduce core body temperature
has been attributed to antipsychotics. Appropriate care is advised
for patients who may exercise strenuously, be exposed to extreme
heat, receive concomitant medication with anticholinergic activity,
or be subject to dehydration.

Esophageal dysmotility and aspiration have been associated with
antipsychotic drug use, including Abilify; use caution in patients
at risk for aspiration pneumonia.

The possibility of a suicide attempt is inherent in psychotic
illnesses, bipolar disorder, and major depressive disorder, and
close supervision of high-risk patients should accompany drug
therapy.

Physicians should advise patients to avoid alcohol while taking
Abilify.

Please see FULL PRESCRIBING INFORMATION, including Boxed
WARNINGS, for Abilify.

About Otsuka Pharmaceutical Co., Ltd. and Bristol-Myers Squibb

Otsuka Pharmaceutical Co., Ltd. and Bristol-Myers Squibb are
collaborative partners in the development and commercialization of
Abilify in the United States and major European countries.

Abilify was discovered by Otsuka Pharmaceutical Co., Ltd.
Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a global
healthcare company with the corporate philosophy: "Otsuka -- people
creating new products for better health worldwide." Otsuka
researches, develops, manufactures and markets innovative and
original products, with a focus on pharmaceutical products for the
treatment of diseases and consumer products for the maintenance of
everyday health. Otsuka is committed to being a corporation that
creates global value, adhering to the high ethical standards
required of a company involved in human health and life,
maintaining a dynamic corporate culture, and working in harmony
with local communities and the natural environment. The Otsuka
Pharmaceutical Group comprises 99 companies and employs
approximately 31,000 people in 18 countries and regions worldwide.
Otsuka and its consolidated subsidiaries earned U.S. $7.2 billion
in annual revenues in fiscal 2006.

Bristol-Myers Squibb is a global biopharmaceutical and related
healthcare products company whose mission is to extend and enhance
human life.

* The Y-MRS is a standard measure that is an 11-item rating
scale used by healthcare providers to assess the scope and severity
of manic symptoms.(1) Y-MRS Total Scores range from 0 (no manic
symptoms) to 60 (severe mania).(2)

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